Evolution of a Pulmonary Insulin Delivery System ( Exubera) for Patients With Diabetes

Priscilla A. Hollander, MD


March 05, 2007

Other Inhaled Insulin Systems in Development

There are a few additional inhaled insulin systems that are earlier in their development process than INH. In one study,[35] either TI or SC insulin was administered to patients (N = 12) with type 2 diabetes, and the relationship between time, insulin concentration, and the glucose elimination rate (GER) was evaluated during a euglycemic clamp study. Patients achieved a greater maximal concentration of insulin at a more rapid rate with TI compared with SC insulin. Maximal GER values were achieved faster with TI, but once a maximal insulin effect occurred, the concentration-effect relationship to GER was similar for TI and SC insulin. The efficacy and safety of TI were assessed in a randomized, double-blind, placebo-controlled study[36] in patients with type 2 diabetes (N = 119) inadequately controlled on diet or oral agents. TI significantly improved HbA1c from baseline compared with placebo (mean change from baseline, -0.72% vs -0.31%, P = .0016), and no severe hypoglycemia was observed in the TI group. There were no differences between groups in pulmonary function (ie, FEV1, DLCO, and total alveolar volume), and no induction of insulin antibodies in the TI group during the 12-week study.

Delivery of human insulin inhalation powder (HIIP) with the Lilly/Alkermes inhaled insulin system had a similar rapid onset, a significantly prolonged duration of action (P < .001), and was tolerated as well as SC insulin lispro in an open-label, randomized, 7-period, euglycemic glucose clamp crossover study[37] in healthy subjects (N = 20). In a randomized, open-label, crossover study,[38] patients with type 1 diabetes received HIIP via the Lilly/Alkermes system or SC insulin + insulin glargine once daily for 12 weeks. Treatment with HIIP appeared to be as safe and as effective as SC insulin in the maintenance of HbA1c levels. Eighty percent of patients (94 of 119) with type 1 diabetes preferred HIIP for mealtime insulin over SC insulin in a randomized, crossover study[39] with the SF-36 Vitality Scale, subscales of the Diabetes Symptom Checklist-Revised, and the Insulin Delivery System Questionnaire at baseline, crossover, and end-of-study scores. A patient-reported (N = 119) outcome study[40] demonstrated that patient satisfaction was improved with HIIP compared with SC insulin, on the basis of significant improvements in treatment satisfaction and greater insulin delivery system satisfaction.

The onset and duration of action of inhaled insulin via the AERx iDMS was compared with SC insulin aspart and SC human regular insulin in a single-center, open-label, 3-period, crossover study[41] in patients (N = 15) with type 1 diabetes. Results from this study demonstrated that inhaled insulin via the AERx iDMS has an onset of action similar to SC insulin aspart, but faster than human regular insulin; however, the duration of action was similar to regular human insulin, but longer than insulin aspart. In patients with type 2 diabetes (N = 107) receiving evening NPH insulin, preprandial inhaled insulin administered via AERx iDMS (n = 54) resulted in similar glycemic control as preprandial SC insulin (n = 53; 7.84% ± 0.77% vs 7.76% ± 0.77%, P = .60) in a randomized, 12-week, open-label, parallel, multicenter, international study.[42] Fasting serum glucose levels were significantly lower for the AERx iDMS group than the SC insulin group (8.9 ± 3.8 mmol/L vs 10.8 ± 3.7 mmol/L, P = .01) at 12 weeks. There were no significant differences between the groups for treatment-emergent adverse events, including pulmonary function. The median total insulin antibody level increased in the AERx iDMS group (6% to 35%) but remained unchanged in the SC group (10% to 9%). There were no correlations between changes in total insulin antibody levels and metabolic control or insulin dose.


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